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Search: WFRF:(Larsson Susanna C) > Carter Paul > Di Angelantonio Emanuele > ACE inhibition and ...

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ACE inhibition and cardiometabolic risk factors, lung ACE2 and TMPRSS2 gene expression, and plasma ACE2 levels : a Mendelian randomization study

Gill, Dipender (author)
Imperial Coll London, St Marys Hosp, Dept Epidemiol & Biostatist, Med Sch Bldg, London, England.
Arvanitis, Marios (author)
Johns Hopkins Univ, Div Cardiol, Dept Med, Baltimore, MD USA.
Carter, Paul (author)
Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
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Cordero, Ana I. Hernandez (author)
Univ British Columbia, St Pauls Hosp, Ctr Heart Lung Innovat, Vancouver, BC, Canada.
Jo, Brian (author)
Lewis Sigler Inst Integrat Biol, Program Quantitat & Computat Biol, Princeton, NJ USA.
Karhunen, Ville (author)
Imperial Coll London, St Marys Hosp, Dept Epidemiol & Biostatist, Med Sch Bldg, London, England.
Larsson, Susanna C. (author)
Karolinska Institutet,Uppsala universitet,Ortopedi,Karolinska Inst, Unit Cardiovasc & Nutr Epidemiol, Inst Environm Med, Stockholm, Sweden
Li, Xuan (author)
Univ British Columbia, St Pauls Hosp, Ctr Heart Lung Innovat, Vancouver, BC, Canada.
Lockhart, Sam M. (author)
Univ Cambridge, Med Res Council, Wellcome Trust Med Res Council Inst Metab Sci, Metab Dis Unit, Cambridge, England.
Mason, Amy (author)
Univ Cambridge, Dept Publ Hlth & Primary Care, British Heart Fdn, Cardiovasc Epidemiol Unit, Cambridge, England.;Uppsala Univ, Natl Inst Hlth Res, Cambridge Biomed Res Ctr, Cambridge, England.;Cambridge Univ Hosp, Cambridge, England.
Pashos, Evanthia (author)
Pfizer Worldwide Res Dev & Med, Internal Med Res Unit, Cambridge, MA USA.
Saha, Ashis (author)
Johns Hopkins Univ, Dept Comp Sci, Baltimore, MD USA.
Tan, Vanessa Y. (author)
Univ Bristol, Med Res Council Integrat Epidemiol Unit, Bristol, Avon, England.;Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol, Avon, England.
Zuber, Verena (author)
Imperial Coll London, St Marys Hosp, Dept Epidemiol & Biostatist, Med Sch Bldg, London, England.;Univ Cambridge, Cambridge Inst Publ Hlth, Med Res Council, Biostat Unit, Cambridge, England.
Bosse, Yohan (author)
Univ Laval, Inst Univ Cardiol & Pneumol Quebec, Laval, PQ, Canada.
Fahle, Sarah (author)
Univ Cambridge, Dept Publ Hlth & Primary Care, British Heart Fdn, Cardiovasc Epidemiol Unit, Cambridge, England.;Univ Cambridge, Natl Inst Hlth Res, Blood & Transplant Res Unit Donor Hlth & Genom, Cambridge, England.;Uppsala Univ, Natl Inst Hlth Res, Cambridge Biomed Res Ctr, Cambridge, England.;Cambridge Univ Hosp, Cambridge, England.
Hao, Ke (author)
Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, Icahn Inst Data Sci & Genom Technol, New York, NY 10029 USA.
Jiang, Tao (author)
Univ Cambridge, Dept Publ Hlth & Primary Care, British Heart Fdn, Cardiovasc Epidemiol Unit, Cambridge, England.
Joubert, Philippe (author)
Univ Laval, Inst Univ Cardiol & Pneumol Quebec, Laval, PQ, Canada.
Lunt, Alan C. (author)
Imperial Coll London, St Marys Hosp, Dept Epidemiol & Biostatist, Med Sch Bldg, London, England.;Cambridge Inst Publ Hlth, MRC Biostat Unit, Robinson Way, Cambridge CB2 0SR, England.
Ouwehand, Willem Hendrik (author)
Univ Cambridge, Dept Haematol, Cambridge Biomed Campus, Cambridge, England. NHS Blood & Transplant, Biomed Campus, Cambridge, England. Wellcome Sanger Inst, Cambridge, England.
Roberts, David J. (author)
Univ Cambridge, Natl Inst Hlth Res, Blood & Transplant Res Unit Donor Hlth & Genom, Cambridge, England.;NHS Blood & Transplant Oxford Ctr, John Radcliffe Hosp, Level 2, Oxford, England.;Univ Oxford, John Radcliffe Hosp, Radcliffe Dept Med, Oxford, England.
Timens, Wim (author)
Univ Groningen, Dept Pathol & Med Biol, Groningen, Netherlands.
van den Berge, Maarten (author)
Univ Groningen, Groningen Res Inst Asthma, Groningen, Netherlands.;Univ Groningen, COPD, Groningen, Netherlands.;Univ Groningen, Dept Pulmonol, Groningen, Netherlands.;Univ Groningen, Groningen Res Inst Asthma, Groningen, Netherlands.;Univ Groningen, COPD, Groningen, Netherlands.
Watkins, Nicholas A. (author)
Univ Cambridge, Natl Inst Hlth Res, Blood & Transplant Res Unit Donor Hlth & Genom, Cambridge, England.
Battle, Alexis (author)
Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA.;Johns Hopkins Univ, Ctr Computat Biol, Baltimore, MD USA.
Butterworth, Adam S. (author)
Univ Cambridge, Dept Publ Hlth & Primary Care, British Heart Fdn, Cardiovasc Epidemiol Unit, Cambridge, England.;Univ Cambridge, Natl Inst Hlth Res, Blood & Transplant Res Unit Donor Hlth & Genom, Cambridge, England.;Univ Cambridge, British Heart Fdn Ctr Res Excellence, Cambridge, England.;Uppsala Univ, Natl Inst Hlth Res, Cambridge Biomed Res Ctr, Cambridge, England.;Cambridge Univ Hosp, Cambridge, England.;Wellcome Genome Campus, Hlth Data Res UK Cambridge, Cambridge, England.;Univ Cambridge, Cambridge, England.
Danesh, John (author)
Univ Cambridge, Dept Publ Hlth & Primary Care, British Heart Fdn, Cardiovasc Epidemiol Unit, Cambridge, England.;Univ Cambridge, Natl Inst Hlth Res, Blood & Transplant Res Unit Donor Hlth & Genom, Cambridge, England.;Univ Cambridge, British Heart Fdn Ctr Res Excellence, Cambridge, England.;Uppsala Univ, Natl Inst Hlth Res, Cambridge Biomed Res Ctr, Cambridge, England.;Cambridge Univ Hosp, Cambridge, England.;Wellcome Genome Campus, Hlth Data Res UK Cambridge, Cambridge, England.;Univ Cambridge, Cambridge, England.
Di Angelantonio, Emanuele (author)
Univ Cambridge, Dept Publ Hlth & Primary Care, British Heart Fdn, Cardiovasc Epidemiol Unit, Cambridge, England.;Univ Cambridge, Natl Inst Hlth Res, Blood & Transplant Res Unit Donor Hlth & Genom, Cambridge, England.;Univ Cambridge, British Heart Fdn Ctr Res Excellence, Cambridge, England.;Uppsala Univ, Natl Inst Hlth Res, Cambridge Biomed Res Ctr, Cambridge, England.;Cambridge Univ Hosp, Cambridge, England.;Wellcome Genome Campus, Hlth Data Res UK Cambridge, Cambridge, England.;Univ Cambridge, Cambridge, England.
Engelhardt, Barbara E. (author)
Princeton Univ, Comp Sci Dept, Princeton, NJ 08544 USA.;Princeton Univ, Ctr Stat & Machine Learning, Princeton, NJ 08544 USA.
Peters, James E. (author)
Wellcome Genome Campus, Hlth Data Res UK Cambridge, Cambridge, England.;Univ Cambridge, Cambridge, England.;Imperial Coll London, Dept Immunol & Inflammat, Fac Med, London, England.
Sin, Don D. (author)
Univ British Columbia, St Pauls Hosp, Ctr Heart Lung Innovat, Vancouver, BC, Canada.
Burgess, Stephen (author)
Univ Cambridge, Med Res Council, Wellcome Trust Med Res Council Inst Metab Sci, Metab Dis Unit, Cambridge, England.;Univ Cambridge, Dept Publ Hlth & Primary Care, British Heart Fdn, Cardiovasc Epidemiol Unit, Cambridge, England.;Univ Cambridge, Cambridge Inst Publ Hlth, Med Res Council, Biostat Unit, Cambridge, England.;Univ Cambridge, British Heart Fdn Ctr Res Excellence, Cambridge, England.;Univ Cambridge, Homerton Coll, Cambridge, England.;Uppsala Univ, Natl Inst Hlth Res, Cambridge Biomed Res Ctr, Cambridge, England.;Cambridge Univ Hosp, Cambridge, England.
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Imperial Coll London, St Marys Hosp, Dept Epidemiol & Biostatist, Med Sch Bldg, London, England Johns Hopkins Univ, Div Cardiol, Dept Med, Baltimore, MD USA. (creator_code:org_t)
2020-11-18
2020
English.
In: Royal Society Open Science. - : ROYAL SOC. - 2054-5703. ; 7:11
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2 have been implicated in cell entry for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). The expression of ACE2 and TMPRSS2 in the lung epithelium might have implications for the risk of SARS-CoV-2 infection and severity of COVID-19. We use human genetic variants that proxy angiotensin-converting enzyme (ACE) inhibitor drug effects and cardiovascular risk factors to investigate whether these exposures affect lung ACE2 and TMPRSS2 gene expression and circulating ACE2 levels. We observed no consistent evidence of an association of genetically predicted serum ACE levels with any of our outcomes. There was weak evidence for an association of genetically predicted serum ACE levels with ACE2 gene expression in the Lung eQTL Consortium (p = 0.014), but this finding did not replicate. There was evidence of a positive association of genetic liability to type 2 diabetes mellitus with lung ACE2 gene expression in the Gene-Tissue Expression (GTEx) study (p = 4 x 10(-4)) and with circulating plasma ACE2 levels in the INTERVAL study (p = 0.03), but not with lung ACE2 expression in the Lung eQTL Consortium study (p = 0.68). There were no associations of genetically proxied liability to the other cardiometabolic traits with any outcome. This study does not provide consistent evidence to support an effect of serum ACE levels (as a proxy for ACE inhibitors) or cardiometabolic risk factors on lung ACE2 and TMPRSS2 expression or plasma ACE2 levels.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kardiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)

Keyword

COVID-19
Mendelian randomization
angiotensin-converting enzyme inhibitors
genetic epidemiology

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